The elucidation of how lysozyme exerts its muramidase, "lectin-like", cationic and hydrophobic effects to fulfill its rule in host defense continues to be the main objective of our research. Through an in-depth in vitro and in vivo investigation of lysozyme's growth inhibitory, bactericidal, bacteriolytic, bacterial aggregating, dechaining, phagocyte enhancing and neutrophil modulting properties, a better understanding of lysozyme's importance in dental caries and periodontal disease should emerge. A second long-term objective of our studies has been to understand the biological function of the human salivary histidine-rich polypeptides (HRP). In preliminary investigations, the HRP have been shown to exhibit antibacterial potential thus confirming our original hypothesis on the similarity of HRP to leukocyte cationic proteins. Specific aims for the project years include (1) immunoadsorption affinity chromatography purification and biochemical and biological characterization of human lysozymes from parotid saliva, submandibular saliva, neutrophils and urine of leukemic patients (2) isolation of the HRP from submandibular saliva by Sephadex G25 chromatography and purification of individual HRP from both parotid and submandibular saliva by high performance liquid chromatography (3) antibacterial studies which will be expanded for testing of lysozyme-depleted and lysozyme-reconstituted salivas and neutrophil extracts; "trypsin-like" enzymes in saliva; sodium bicarbonate and fluoride lytic potential in the acidic pH region and; effects on the caries process through in vitro contact microradiographic assays (4) assessment of the role of autolysins in bacteriolytic, dechaining, and bactericidal effects of lysozyme, HRP, inorganic anions and trypsin (5) determination of the molecular nature of the interaction of lysozyme with purified lipoteichoic acid (LTA) and bacterial cell wall carbohydrates through quantitative binding studies (6) development of a sensitive ELISA technique and correlation of lysozyme concentrations in the salivas and plaques of caries susceptible and caries resistant individuals with the extent of plaque streptococcal dechaining and (7) determination of whether lysozyme can enhance phagocytosis of peridontopathic microorganisms and inhibit chemotaxis in an in vivo assay system measuring the migration of gingival leukocytes.